Regorafenib in Combination With Pembrolizumab or Pembrolizumab for MSI-H Colorectal Cancer

NCT06006923 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: HCC 23-041
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a trial of Regorafenib in combination with pembrolizumab for patients with MSI-H colorectal cancer consisting of lead-in phase examining preliminary efficacy and safety, followed by a randomized phase to further examine efficacy.

Conditions

MSI-H Colorectal Cancer

Keywords

multi-kinase inhibitor; receptor tyrosine kinases; anti-PD1 blockade; immune checkpoint inhibitor; vascular endothelial growth factor receptor (VEGFR)

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR), Lead-in Phase

  Percentage of patients with partial response (PR) or complete response (CR) to the treatment per RECIST 1.1. criteria. v1.1. Per RECIST v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or nontarget) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 12 months (lead-in phase)

• Progression-free Survival (PFS), Randomize Phase

  Median number of months from time of randomization to the date of disease progression or death from any cause. Per RECISIT v1.1: Progressive Disease (PD):≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.

  Up to 24 months

Secondary Outcomes (6)

• Adverse Events and Serious Adverse Events Related to Treatment

  Up to 24 months (lead-in phase)

• Adverse Events and Serious Adverse Events Related to Treatment

  Up to 24 months (beginning at start of post lead-in phase)

• Progression-free Survival (PFS), Lead-In Phase

  Up to 24 months

• Overall Survival (OS)

  Up to 48 months (lead-in phase)

• Overall Survival (OS)

  Up to 24 months (beginning at start of post lead-in phase)

Study Arms (2)

Pembrolizumab + Regorafenib

EXPERIMENTAL

Pembrolizumab: 200mg, Q3 weeks Regorafenib: 60mg Cycle 1 Day 1 90 mg Cycle 2 Day 1

Drug: Regorafenib; Drug: Pembrolizumab

Pembrolizumab

ACTIVE COMPARATOR

Pembrolizumab: 200mg, Q3 weeks

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

An anti-PD1 blockade / immune checkpoint inhibitor treatment approved for patients with high microsatellite instability (MSI-H) colorectal cancer (CRC) as first line therapy.

Also known as: Keytruda

Pembrolizumab; Pembrolizumab + Regorafenib

Regorafenib DRUG

A multi-kinase inhibitor that targets several receptor tyrosine kinases including vascular endothelial growth factor receptor (VEGFR), which may also have immunomodulatory affect in the tumor microenvironment.

Also known as: BAY 73-4506, Stivarga

Pembrolizumab + Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed mismatch repair deficient or microsatellite instability high advanced stage colorectal cancer
• Measurable disease (per RECIST v1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Age \> 18
• The patient must be able to swallow oral medication.
• Adequate organ function based on the following lab assessments:
• ANC must be ≥ 1500/mm3
• platelet count must be ≥ 100,000/mm3
• WBC count ≥ 2.5 × 109 /L
• Hemoglobin must be ≥ 9 g/dL
• Alkaline phosphatase ≤ 2.5× upper limit of normal (ULN) with the exception of patients with documented liver or bone metastases who should have ALP ≤ 5.0× ULN
• AST and ALT ≤ 2.5× ULN with the exception of patients with documented liver metastases who may have AST and/or ALT ≤ 5.0× ULN
• International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation
• Total bilirubin ≤ 1.5× ULN (≤ 3× ULN if Gilbert syndrome present)
• Serum albumin ≥ 2.8 g/dL or 28 g/L

You may not qualify if:

• Prior anti-programmed death 1 (anti-PD-1) or anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) based therapy
• More than 3 cycles of chemotherapy or progression of disease on first line therapy excluding adjuvant treatment and any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
• Active autoimmune disease
• Pregnant or lactating females
• Uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV); patients with undetectable viral load and CD4 count \> 200 will be eligible for enrollment
• Active untreated brain metastasis
• Uncontrolled hypertension (HTN: systolic pressure \> 150 mmHg or diastolic pressure \> 90 mmHg on repeated measurements) and cardiovascular events within 12 months of start of treatment
• Active infection or chronic infection requiring chronic suppressive antibiotics
• No active cancer such as colon cancer other than adenocarcinoma (e.g., sarcoma, lymphoma, carcinoid) within 1 year
• Patients with severe hepatic impairment (Child-Pugh C) are excluded as regorafenib has not been studied in this population and exposure might be increased in these patients
• Major surgical procedure or significant traumatic injury within 28 days before start of study medication
• Non-healing wound, non-healing ulcer, or non-healing bone fracture
• Patients with evidence or history of any bleeding diathesis, irrespective of severity
• Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication:
• Major surgical procedure or significant traumatic injury within 28 days before start of study medication

Sponsors & Collaborators

• Anwaar Saeed: lead
• Bayer: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

regorafenib; pembrolizumab

Study Officials

• Anwaar H Saeed, MD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine, Chief, Gastrointestinal Medical Oncology

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 23, 2023
• Study Start: June 26, 2024
• Primary Completion: July 11, 2025
• Study Completion: November 12, 2025
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)